Alzheimer disease (AD) refers to a slowly progressive loss of nerve cells (neurons) in the brain. Symptoms of the illness usually unfold slowly over a period of years. Neurons involved in memory and thinking are affected first, while movement and sensation are only affected in the very late stages.
Several different forms of Alzheimer disease have been discovered – a few rare forms are strongly inherited and become symptomatic in mid-life, while the vast majority result from complex interactions between genes and the environment, and do not become symptomatic until late-life.
By definition, all forms of Alzheimer disease share two features in common, namely the abnormal accumulation of two misfolded proteins: 1) beta-amyloid (a-beta) and 2) phosphorylated tau (p-tau). The accumulation of these proteins may result from either over-production in or decreased clearance from the brain.
A-beta amyloid proteins accumulate at synapses (sites of inter-neuronal communications) to form amyloid plaques. This process jams the communication of information within complex networks of brain cells. Communication normally involves the release of chemical neurotransmitters from the endings of one nerve cells (pre-synaptic terminals), which then dock at receptors of receiving nerve cells (post-synaptic terminals).
P-tau form helical filaments which are known as "neurofibrillary tangles" within the neuron cell body and “neurites” at nerve cell terminals. This causes problems in the vital transportation of molecules within the nerve cell, which takes place through a system of microtubules akin to those that transport water and nutrients to the leaves of plants and trees.
Billions of neurons and trillions of synapses in the human brain are organized in complex networks specialized for sensory perception and movement, as well as memory and intellectual processing (higher cognitive functions). The networks for higher cognitive function suffer the brunt of damage in Alzheimer disease.
The ability to store new experiences and learn new information is affected first in Alzheimer disease. The earliest signs may be difficult to distinguish from slowing associated with the normal aging process. Even in the best of circumstances, human memory is limited and imperfect. We only remember things that we notice and pay attention to, which is only a fraction of what is taking place around us. We choose to pay attention to things that are personally important to us.
Persons affected by Alzheimer disease, however, have difficulty remembering new information that is of personal importance and despite paying good attention. For example, it is normal to misplace ones keys, if one is not paying attention; but it would be worrisome if someone forgot to pay a large bill or missed an important family event.
Early on, Alzheimer disease also affects executive functions. This includes the ability to actively organize, analyze, and solve problems. Usually people with early Alzheimer disease are not fully aware of the decline in their memory skills and have difficulty judging the impact these changes may have on their safety or day function.
As the illness progresses, decline becomes evident in visual-spatial and language abilities. The combined loss of memory and visual-spatial orientation places a person at greater risk of getting lost in unfamiliar surroundings. This can result in confusing experiences for a person with Alzheimer disease who is walking or driving alone. The person with AD may experience difficulty finding words, understanding complex instructions, or following multiple step commands. Thus, in the mid stages of Alzheimer disease, a person needs increased assistance with activities of daily living and personal care such as dressing, grooming, and bathing. If the illness goes on for many years, independence is lost for most of the functions of daily life. And in the most advanced stages, walking and swallowing are affected. At this point, the person can be at risk for infections such as pneumonia or sepsis.
Changes in mood and behavior, as well as memory loss and thinking, are frequently observed in those with Alzheimer disease, but differ greatly from one person to another. Depression, irritability, defensiveness, and social withdrawal are often noted in the early stages. Suspiciousness, paranoia, and visual hallucinations may develop in the later stages. Various degrees of hyperactivity, agitation, wandering, and sleep disturbances may also occur. These behavioral symptoms can sometimes be improved by thoughtful modifications of interpersonal interactions or changes in the environment. Medications may also be helpful.
Through research, the multiple steps leading to the formation and clearance of these proteins are becoming increasing clear. This knowledge will lead to new ideas about ways to slow down or stop the disease process. The safety and effectiveness of new approaches to treatment are then put to test in carefully-controlled conditions known as clinical trials.
Beta-amyloid protein is known to be toxic to nerve cells. The a-beta protein is clipped out of a large protein known as amyloid protein precursor (APP). It might be possible to treat the disease by changing the activity of the two enzymes, known as beta- and gamma-secretase, responsible for splicing a-beta protein at each end. Drugs currently being studied that exemplify this strategy include R-flurizan, curcumin, and Alzamed.
The whole world awaits the day when a truly effective medical treatment becomes available for Alzheimer Disease. Meanwhile the best treatment is a day-by-day holistic approach to optimize quality of life. A huge difference can be made in the quality of the present moments we experience, depending much upon our outlook and supportive and caring relationships with others. This depends upon maintaining the spiritual, physical, and mental well-being of the care partner, as well as the person with AD. Long-term planning is very important to address physical, financial, and respite needs of the family unit. There are an increasing number of resources and options available in the community to consider. At the present time, an interdisciplinary approach to AD care is ideal.
The Food and Drug Administration (FDA) has approved five medications for the treatment of Alzheimer disease. Four of these belong to the family of medications known as acetylcholinesterase inhibitors: donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), and tacrine (Cognex). The fifth medication, memantine (Namenda) acts as a partial antagonist of the neurotransmitter glutamate. Memantine can be prescribed together with one of the four cholinesterase inhibitors. In general, these medications exert modest beneficial effects. They may hold back symptom progression for 6 to 12 months. However, there is no convincing evidence that they slow down the progression of the underlying disease.
There is some limited evidence that the anti-oxidant vitamin E may slow progression of AD. There is rationale for taking a combination of vitamin E and vitamin C as dual anti-oxidants.
Disturbances of mood and behavior may benefit from psychotropic medications, including anti-depressants such as SSRIs (selective serotonin reuptake inhibitors). Medications originally developed as anti-convulsants may decrease agitation (e.g., valproic acid and gabapentin). Paranoid delusions or visual hallucinations may warrant treatment with atypical neuroleptic medications, such as respirdone, olanzepine, or quetiapine. Because of individual differences in symptoms and physiology, it is often difficult to predict which medication will work best. A dedicated and knowledgeable physician, together with patience during a trial and error process, is often required.